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Biomedical subjects

G Doria

Publications and source records attributed to G Doria.

At least 127 records · Page 7Linked to original sources
PubMed1982

Immunoregulation in senescence: increased inducibility of antigen-specific suppressor T cells and loss of cell sensitivity to immunosuppression in aging mice.

Azobenzenearsonate (ABA)-specific T cell-mediated suppression has been studied in aging mice. ABA-specific suppressor T cells were induced in young and old mice by injection of ABA conjugated to syngeneic spleen cells (ABA-SC). These suppressor cells were tested for their ability to suppress the in vitro anti-trinitrophenyl (TNP) antibody response of lymph node cells obtained from ABA-keyhole limpet hemocyanin (KLH)-primed young or old mice and cultured with TNP-ABA-KLH. Suppressor T cells were found to be more easily induced in old than in young mice but to suppress less efficiently the antibody response of cells from old than from young mice. The increased inducibility of antigen-specific suppressor T cells in old mice is compatible with the age-dependent decline of immune responsiveness to exogenous antigens. The loss of cell sensitivity to antigen-specific immunosuppression as well as the lack of evidence for increased nonspecific suppression in old mice is consistent with the age-related increase in autoimmune disorders. These findings provide a unifying explanation for the most relevant immunological phenomena of senescence.

Aging↗
PubMed1982

T-cell-dependent oscillations of IgM antibody affinity during the immune response to DNP-Dextran to low or high epitope density.

Anti-hapten IgM antibody response and affinity were evaluated by haemolytic plaque inhibition assay on spleen cells from mice immunized with 2,4, dinitrophenyl (DNP)1.3-Dextran or DNP13-Dextran. Regardless of epitope density, affinity was found to mature with time after immunization and to be characterized by rapid oscillations independent of changes in anti-hapten plaque-forming cell (PFC) response and antibody secretion rate. Injection of the lower epitope density immunogen not only elicited higher PFC responses and higher affinity antibodies but also induced more pronounced affinity oscillations mainly confined to the higher affinity PFC subpopulation. Immunization of athymic nude mice with DNP1.3-Dextran elicited PFC responses comparable to those observed in similarly immunized euthymic mice. However, affinity oscillations were drastically reduced in athymic mice and the restricted variation of antibody affinity observed shortly after immunization was followed by no oscillations in any of the affinity PFC subpopulations. Athymic mice did not produce high affinity PFC which account to a large extent for the affinity oscillations observed in euthymic mice. These findings demonstrate the important role of T cells in the appearance of rapid changes in IgM antibody affinity. The generation of T-cell-dependent oscillations of high affinity antibody-producing cell subpopulations is discussed in terms of interactions among cells and soluble factors involved in regulatory circuits of the immune network.

Animals↗
PubMed1981

Production of antigen-specific suppressive T cell factor by radiation leukemia virus-transformed suppressor T cells.

Hen egg-white lysozyme (HEL)-specific suppressor T cells induced in C57BL/6 mice have been selected by sequential passage over plates coated with goat anti-mouse Ig and HEL. These suppressor T cells, 80% I-J+, were infected in vitro with radiation leukemia virus (RadLV/Nu1) and injected intravenously into sublethally irradiated syngeneic recipients. After 4-6 months, 6 out of 20 injected mice developed thymic lymphomas, which were maintained by transplantation into histocompatible hosts and subsequently established as permanent cell lines. Cells of these six thymomas were screened for the presence of Thy 1.2, Lyt 1, Lyt 2, I-Jb, and Ig cell surface antigens by direct or indirect immunofluorescence. One tumor (thymoma L4) was found to express the expected phenotype of suppressor T cells (Thy 1.2+, Lyt 2+, I-J+). High-speed supernatants of extracts obtained from L4 cells were able to induce HEL-specific suppression in a T cell proliferative assay, demonstrating the presence of an antigen-specific suppressive T cell factor.

Animals↗
PubMed1981

Synergism between two helper cell subpopulations characterized by different radiosensitivity and nylon adherence.

The present work extends our previous results on the radiosensitivity of the helper cell function. Two helper cell subpopulations, 1 radiosensitive and the other radioresistant, have been demonstrated in the spleen of mice at different times after priming with HRBC. The radiosensitive subpopulation increases with the increasing time interval between carrier-priming and irradiation. The 2 cell subpopulations have been further characterized by different nylon adherence properties: radioresistant helper cells adhere to nylon wool, whereas radiosensitive cells pass through. The 2 cell subpopulations were separated by x-irradiation and nylon wool filtration, and their helper activity was assessed separately or after recombination. The results favor the notion that 2 functionally independent helper T cells, as characterized by different radiosensitivity and nylon adherence, participate synergistically in the helper activity of primed spleen cells.

Animals↗
PubMed1980

Antiallergic agents. IV - Substituted 2-benzylidene-3(2H)-benzofuranone-5-carboxylic acids.

A series of substituted 2-benzylidene-3(2H)-benzofuranone-5-carboxylic acids were synthetized and tested for antiallergic activity by the passive cutaneous anaphylactic reaction in the rat. Many compounds display an antiallergic activity comparable to that of disodium chromoglycate when administered parenterally: in addition some derivatives are effective when given by mouth.

Animals↗
PubMed1980

Oscillations of IgM antibody affinity at the level of single immunocytes.

IgM antibody affinity was measured by hemolytic plaque inhibition assays on spleen cells from mice immunized with a single injection of DNP-dextran. Maturation of affinity was found to occur with time after 1 to 1000 microgram of immunogen and to be characterized by rapid oscillations independent from changes inFC number/spleen and in antibody secretion rate. Analysis of affinity heterogeneity showed that such oscillations occur in higher affinity PFC subpopulations. The origin of affinity oscillations was discussed in terms of interactions among antigen and the elements of the immune network.

Animals↗
PubMed1978

Time and antigen dose-dependent variations of IgM antibody affinity.

Affinity of IgM antibodies elicited in mice by a single injection of dinitrophenylated dextran was measured by equilibrium dialysis. Maturation of affinity was found to occur with time, the rate of increase being higher after larger antigen doses. Maturation was followed by a decrease of affinity with time, the fall being more pronounced after lower antigen doses. These findings are more in line with the theory of antigen-induced diversity rather than with the maturation theory.

Animals↗
PubMed1978

Radiosensitivity of the helper cell function.

The helper function of T cells primed and irradiated in vivo was tested in vitro by the Mishell-Dutton technique. Spleen cells from mice carrier-primed with HRBC and exposed to 50 to 2000 rads of x-radiation were assayed for their ability to help syngeneic normal spleen cells to mount an in vitro anti-hapten antibody response after stimulation with the conjugate TNP-HRBC. The anti-TNP response was evaluated by the Jerne technique. The helper activity was titrated by adding graded numbers of carrier-primed spleen cells to a constant number of normal spleen cells. The slope of the initial linear portion of the response-cell dose titration curve was taken as an estimated of the helper activity and found to decrease with increasing the x-ray dose. The curve describing the remaining helper activity as a function of the radiation dose shows the presence of two components, one radiosensitive, the other, radioresistant. This suggests the existence either of helper cells at different stages of activation or of two cell subpopulations participating in the helper function.

Animals↗